Hypoglycemia (i.e. abnormally low blood glucose levels) is believed to be the cause of death in about three percent of insulin-treated diabetic patients. The putative mechanism for death due to hypoglycemia is a hypoglycemia-induced prolongation of the QT interval of the intracardiac electrogram (IEGM), which increases the risk of malignant ventricular tachycardia. See, for example, Eckert et al., “Hypoglycemia Leads to an Increased QT Interval in Normal Men,” Clinical Physiology. 1998; 18(6):570-575, and Heller, “Abnormalities of the Electrocardiogram during Hypoglycaemia: The Cause of the Dead in Bed Syndrome,” Int. J. Clin. Pract. 2002; Suppl. 129:27-32. Note that the QT interval represents the portion of the IEGM between the beginning of ventricular depolarization and the end of ventricular repolarization. Ventricular depolarization is manifest within the IEGM as a QRS complex (sometimes also referred to as an R-wave.) The QRS complex usually follows an atrial depolarization (also referred to as a P-wave.) Ventricular repolarization is manifest within the IEGM as a T-wave. Note also that the terms P-wave, R-wave and T-wave are also commonly used to refer to features of surface electrocardiograms (ECGs). Herein, the terms refer to the corresponding internal signal components.
In adults, if not treated properly, severe hypoglycemia may result in coma and irreversible brain damage. See, Jones et al., “Mild Hypoglycemia and Impairment of Brain Stem and Cortical Evoked Potentials In Healthy Subjects,” DIABETES 1990; 39:1550-1555. Even in cases where hypoglycemia does not cause severe consequences, it is often the limiting factor in achieving effective glycemic control in patients with diabetes, particular insulin-depended diabetics. In this regard, patients sometimes refrain from taking prescribed dosages of insulin for fear that the insulin might trigger an episode of hypoglycemia, which can be quite unpleasant. Failure to take the prescribed insulin prevents the patient from maintaining glycemic levels within a healthy range, thus often leading to additional health problems. Hypoglycemia is also a serious and frequent problem in patients suffering hyperinsulinism, wherein the body generates too much insulin, thereby triggering episodes of hypoglycemia even if an otherwise sufficient amount of sugar or other glucose-generating substances are ingested.
In view of the adverse consequences of hypoglycemia, particularly within insulin-dependent diabetic patients or hyperinsulinism patients, it is highly desirable to provide techniques for detecting hypoglycemia within such patients and automatically delivering appropriate therapy or warning signals. It is known that hypoglycemia can be detected based on observation of changes in the QT interval observed within an ECG, as well as based on observation of dispersion of QT intervals within the ECG (based on studies involving experimental hypoglycemia within adults with type 1 diabetes, i.e. diabetes wherein the body does not make insulin or at least doe not make enough insulin.) Studies in diabetics have also shown that hypoglycemia can be detected based on the observation of a significant lengthening of the QTc interval occurring during spontaneous nocturnal hypoglycemia. See, Robinson et al., “Changes In Cardiac Repolarization During Clinical Episodes Of Nocturnal Hypoglycaemia In Adults With Type 1 Diabetes” Diabetologia 2004; 47:312-5. The QTc interval is an adjusted version of the QT interval that has been corrected to a heart rate of 60 beats per minute (bpm). See, also, U.S. Pat. No. 6,572,542 to Houben, et al., entitled “System and Method for Monitoring and Controlling the Glycemic State of a Patient,” which describes a technique exploiting a combination of ECG signals and electroencephalogram (EEG) for the detection of hypoglycemia.
Accordingly, various techniques have been developed for detecting hypoglycemia based on ECG signals. However, it is desirable to provide effective techniques for detecting hypoglycemia based on IEGM signals so that detection may be performed by an implantable medical device without requiring surface electrodes. In particular, it is desirable to provide techniques for detecting hypoglycemia (or for detecting blood glucose levels so that hypoglycemia may be detected therefrom) for use with pacemakers or ICDs, as many patients at risk of hypoglycemia are also candidates for pacemakers and/or ICDs and such devices routinely detect the IEGM for use in pacing the heart and detecting arrhythmias
One effective technique for detecting blood glucose levels based on IEGM signals sensed by an implantable medical device is set forth in U.S. Patent Application Serial Number 2004/0077962 of Kroll, published Apr. 22, 2004, entitled “System and Method for Monitoring Blood Glucose Levels Using an Implantable Medical Device.” Briefly, with the technique of Kroll, blood glucose levels are determined by an implantable device based on IEGM signals by detecting and examining a combination of T-wave amplitude fraction and QTc interval. The technique may also be used to detect hypoglycemia based on changes in blood glucose levels. Another effective technique for use with implantable devices is set forth in U.S. Patent Application 2006/0167517, of Gill et al., filed Jan. 25, 2005, entitled “System and Method for Distinguishing among Cardiac Ischemia, Hypoglycemia and Hyperglycemia using an Implantable Medical Device.” Briefly, techniques are described therein for detecting and distinguishing ischemia, hypoglycemia and hyperglycemia based on IEGM signals. Hypoglycemia is detected based on a change in ST segment elevation along with a lengthening of either the interval between the QRS complex and the peak of the T-wave (QTmax) or the interval between the QRS complex and the end of the T-wave (QTend). By exploiting QTmax and QTend in combination with ST segment elevation, changes in ST segment elevation caused by hypoglycemia can be properly distinguished from changes caused by ischemia or hyperglycemia.
See, also, U.S. Patent Application 2006/0167518, entitled “System and Method for Distinguishing among Cardiac Ischemia, Hypoglycemia and Hyperglycemia using an Implantable Medical Device” and 2006/0167519, also entitled “System and Method for Distinguishing Among Cardiac Ischemia, Hypoglycemia and Hyperglycemia Using an Implantable Medical Device,” both to Gill et al., and Ser. No. 11/740,175, filed Apr. 25, 2007, entitled “System and Method for Efficiently Distinguishing among Cardiac Ischemia, Hypoglycemia and Hyperglycemia Using an Implantable Medical Device and an External System,” to Fard et al. Still further, see hypoglycemia detection techniques discussed in: U.S. Patent Application 2006/0167365, of Bharmi, filed May 11, 2005, entitled “System and Method for Distinguishing Between Hypoglycemia and Hyperglycemia using an Implantable Medical Device”; U.S. Patent Application 2006/0247685 also of Bharmi, filed Apr. 27, 2005, entitled “System and Method for Detecting Hypoglycemia Based on a Paced Depolarization Integral Using an Implantable Medical Device”; and U.S. patent application Ser. No. 11/757,796, filed Jun. 4, 2007, of Boileau et al., entitled “System and Method for Adaptively Adjusting Cardiac Ischemia Detection Thresholds and Other Detection Thresholds used by an Implantable Medical Device.”
Although the techniques of the aforementioned patent applications are effective, it would be desirable to provide still other techniques for detecting hypoglycemia using an implantable medical device and it is to that end that aspects of the present invention are directed. In particular, it is desirable to provide techniques for detecting pre-symptomatic hypoglycemia, i.e. before symptoms are manifest, so as to warn the patient, and other aspects of the invention are directed to that end. In this regard, patients may only become truly symptomatic well after blood glucose levels have dropped into the hypoglycemic range. In the absence of pre-symptomatic warnings, the patients would have to depend on symptoms to know that a hypoglycemic event is ongoing, which thus delays any needed medical attention. Relying on symptoms is even more problematic in patients who have had earlier episodes of hypoglycemia, as such patients can become desensitized to the symptoms of hypoglycemia. Also, the majority of hypoglycemic events may occur while the patient is sleeping when the symptoms are minimal or unnoticeable. Hence, a technique providing for pre-symptomatic detection of hypoglycemia would be particularly advantageous.